1. Field of the Invention
This invention relates to the synthesis of N—[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester (neotame) using 3,3-dimethylbutyraldehyde precursors. This method of producing neotame is more simple and more economical than the conventional preparation of neotame.
2. Related Background Art
N—[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester (neotame) is a high potency dipeptide sweetener (about 8000× sweeter than sucrose) that has the formula

The chemical synthesis of neotame is disclosed in U.S. Pat. No. 5,480,668, U.S. Pat. No. 5,510,508, U.S. Pat. No. 5,728,862 and WO 00/15656, the disclosure of each of which is incorporated by reference herein.
U.S. Pat. Nos. 5,510,508 and 5,728,862 describe the synthesis of neotame by hydrogenation of a mixture of aspartame and 3,3-dimethylbutyraldehyde with a catalyst such as Pd on carbon. This synthesis is represented by the following equation.

The 3,3-dimethylbutyraldehyde used in this synthesis is typically produced from the bisulfite adduct of 3,3-dimethylbutyraldehyde by treatment with base, followed by distillation as described in U.S. Pat. No. 5,905,175, the disclosure of which is incorporated by reference herein. The above-noted neotame process requires the reaction of pure isolated aspartame with pure isolated aldehyde to produce neotame. However, it would be economically advantageous to use 3,3-dimethylbutyraldehyde precursors directly in neotame synthesis without having to first isolate 3,3-dimethylbutyraldehyde in order to economically and efficiently produce pure N—[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.